Mothers' prenatal stress and their children's antisocial outcomes – a moderating role for the Dopamine D4 Receptor ( DRD 4) gene
Open accessAbstract
Background: Maternal distress during pregnancy has been linked to aggressive behavior in offspring. This effect has been interpreted in terms of ‘fetal programming’. The 7‐repeat (7r) allele of a VNTR polymorphism in exon III of the human dopamine receptor D4 ( DRD 4) has consistently been associated with externalizing behavior problems, especially in the presence of adverse environmental factors. So far, it is not known whether the DRD 4 genotype moderates the effect of prenatal maternal stress on the development of childhood antisocial behavior. Methods: As part of an ongoing epidemiological cohort study, prenatal maternal stress was assessed using self‐report 3 months following child birth. When children were 8, 11, and 15 years old, mothers rated their children's externalizing behavior, and diagnoses of conduct disorder and/or oppositional defiant disorder ( CD / ODD ) according to DSM ‐ IV were obtained. In a sample of N = 308 participants, the effects of the DRD 4 genotype, prenatal maternal stress, and the interaction thereof on antisocial outcome were tested. Results: Under conditions of elevated prenatal maternal stress, children carrying one or two DRD 4 7r alleles were at increased risk of a diagnosis of CD / ODD . Moreover, homozygous carriers of the DRD 4 7r allele displayed more externalizing behavior following exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD 4 4r allele turned out to be insensitive to the effects of prenatal stress. Conclusions: This study is the first to report a gene–environment interaction related to DRD 4 and prenatal maternal stress using data from a prospective study, which extends earlier findings on the impact of prenatal maternal stress with respect to childhood antisocial behavior.
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Homozygous 4 R carriers were insensitive to prenatal stress.
“Homozygous 4 R carriers -> insensitive to prenatal stress”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Zohsel [84]
There was a gene-environment interaction: homozygous 7 R carriers with increased prenatal stress showed increased externalizing behaviors.
“GxE: Homozygous 7 R carriers + increased prenatal stress -> increased externalizing behaviors”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Zohsel [84]
Larger repeat allele (7 R or 6-8 R)-carrying DRD4 genotypes were associated with higher externalizing behaviors or aggression compared to 7 R non-carrying genotypes only in the context of maternal insensitivity, high maternal prenatal stress, or low-aggression peer play environment.
“More specifically, larger repeat allele (7 R or 6-8 R)-carrying genotypes were associated with higher externalizing behaviors or aggression compared to 7 R non-carrying genotypes (e.g., 2–4 R) only in the context of maternal insensitivity [83], high maternal prenatal stress [84], or low-aggression peer play environment [85].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [84]
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- Authors
- Zohsel, K., Buchmann, A. F., Blomeyer, D., Hohm, E., Schmidt, M. H., Esser, G., Brandeis, D., Banaschewski, T., & Laucht, M.
- Affiliations
- Heidelberg University (DE)
- University of Potsdam (DE)
- University of Zurich (CH)
- Corresponding author
- Laucht, Manfred
- Venue
- Journal of Child Psychology and Psychiatry
- Publisher
- Wiley
- Published
- 2013-09-14
- Volume
- 55
- Issue
- 1
- Pages
- 69-76
- ISSN
- 0021-9630 (ISSN-L)
- 1469-7610
- OpenAlex
- W2041158650
- Cited by
- 68
- References
- 36
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 16 · 2014: 8
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Journal of Child Psychology and Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- publish.UP (University of Potsdam) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- prenatal stress, dopamine D4 receptor gene, gene-environment interaction, childhood antisocial behavior, conduct disorder, oppositional defiant disorder, externalizing problems, fetal programming
- MeSH terms
- Adolescent, Adult, Child, Female, Genotype, Humans, Infant, Male, Mothers, Pregnancy, Prenatal Exposure Delayed Effects, Prospective Studies, Stress, Psychological, Conduct Disorder, Attention Deficit and Disruptive Behavior Disorders, Receptors, Dopamine D4, Gene-Environment Interaction
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